Associations between children's family environment, spontaneous brain oscillations, and emotional and behavioral problems.

The family environment in childhood has a strong effect on mental health outcomes throughout life. This effect is thought to depend at least in part on modifications of neurodevelopment trajectories. In this exploratory study, we sought to investigate whether a feasible resting-state fMRI metric of local spontaneous oscillatory neural activity, the fractional amplitude of low-frequency fluctuations (fALFF), is associated with the levels of children's family coherence and conflict. Moreover, we sought to further explore whether spontaneous activity in the brain areas influenced by family environment would also be associated with a mental health outcome, namely the incidence of behavioral and emotional problems. Resting-state fMRI data from 655 children and adolescents (6-15 years old) were examined. The quality of the family environment was found to be positively correlated with fALFF in the left temporal pole and negatively correlated with fALFF in the right orbitofrontal cortex. Remarkably, increased fALFF in the temporal pole was associated with a lower incidence of behavioral and emotional problems, whereas increased fALFF in the orbitofrontal cortex was correlated with a higher incidence.

Effects of the brain-derived neurotropic factor variant Val66Met on cortical structure in late childhood and early adolescence.

BACKGROUND: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been associated with several neuropsychiatric disorders and regional structural brain changes in adults, but little is known about Val66Met's effect on brain morphology during typical or atypical neurodevelopment. Windows of vulnerability to psychopathology may be associated with the different alleles of the Val66Met polymorphism during childhood and adolescence. METHODOLOGY: We investigated the effect of Val66Met on cortical thickness in MRI scans of 718 children and adolescents (6-12 years old) with typical development, and in those meeting DSM criteria for a psychiatric disorder. RESULTS: Val66Met had a significant effect on cortical thickness. Considering the typically developing group, Met-carriers presented thicker parietal and occipital lobes and prefrontal cortices compared to Val homozygotes. Met-carriers with psychiatric disorders presented thicker medial and lateral temporal cortices than Val homozygotes. Furthermore, a significant genotype × psychiatric diagnosis interaction was found: Met-carriers with a psychiatric diagnosis presented thinner bilateral prefrontal cortices than Val homozygotes. CONCLUSION: This study provides evidence that Val66Met is associated with cortical maturation in children and adolescents with and without psychiatric disorders.

Association between abnormal brain functional connectivity in children and psychopathology: A study based on graph theory and machine learning.

OBJECTIVES: One of the major challenges facing psychiatry is how to incorporate biological measures in the classification of mental health disorders. Many of these disorders affect brain development and its connectivity. In this study, we propose a novel method for assessing brain networks based on the combination of a graph theory measure (eigenvector centrality) and a one-class support vector machine (OC-SVM). METHODS: We applied this approach to resting-state fMRI data from 622 children and adolescents. Eigenvector centrality (EVC) of nodes from positive- and negative-task networks were extracted from each subject and used as input to an OC-SVM to label individual brain networks as typical or atypical. We hypothesised that classification of these subjects regarding the pattern of brain connectivity would predict the level of psychopathology. RESULTS: Subjects with atypical brain network organisation had higher levels of psychopathology (p < 0.001). There was a greater EVC in the typical group at the bilateral posterior cingulate and bilateral posterior temporal cortices; and significant decreases in EVC at left temporal pole. CONCLUSIONS: The combination of graph theory methods and an OC-SVM is a promising method to characterise neurodevelopment, and may be useful to understand the deviations leading to mental disorders.

Low frequency fluctuation of brain spontaneous activity and obsessive-compulsive symptoms in a large school-age sample.

BACKGROUND: The present study was designed to explore alterations in brain dynamics at rest that are associated with Obsessive Compulsive Symptoms (OCS) in childhood by measuring low frequency fluctuation of spontaneous brain activity in a large school community sample from a developing country. METHOD: Resting state functional magnetic resonance imaging data were collected in a sample of 655 children and adolescents (6-15 years old) from the brazilian 'High Risk Cohort Study for Psychiatric Disorders (HRC)'. OCS were assessed using items from the Compulsion and Obsessions section of the Development and Well-Being Assessment (DAWBA). The correlation between the fractional amplitude of low frequency fluctuations (fALFF) and the number of OCS were explored by using a general linear model, considering fALFF as response variable, OCS score as regressor and age, gender and site as nuisance variables. RESULTS: The number of OCS was positively correlated with the fALFF coefficients at the right sensorimotor cortex (pre-motor, primary motor cortex and post-central gyrus) and negatively correlated with the fALFF coefficients at the insula/superior temporal gyrus of both hemispheres. Our results were specific to OCS and not due to associations with overall psychopathology. CONCLUSIONS: Our results suggest that brain spontaneous activity at rest in the sensorimotor and insular/superior-temporal cortices may be involved in OCS in children. These findings need independent replication and future studies should determine whether brain spontaneous activity changes within these regions might be predictors of risk for obsessive-compulsive disorder latter in life.

Children with Poor Reading Skills at the Word Level Show Reduced Fractional Anisotropy in White Matter Tracts of Both Hemispheres.

Diffusion tensor imaging (DTI) studies showed that microstructural alterations are correlated to reading skills. In this study, we aim to investigate white matter microstructure of a group of Portuguese speakers with poor reading level, using different parameters of DTI. To perform this analysis, we selected children ranging from 8 to 12 years of age, poor readers (n = 17) and good readers (n = 23), evaluated in the word-level ability based on a Latent Class Analysis (LCA) of Academic Performance Test (TDE). Poor readers exhibited significant fractional anisotropy (FA) reductions in many tracts of both hemispheres, but small and restricted clusters of increased radial diffusivity (RD) in the left hemisphere. Spatial coherence of fibers might be the main source of differences, as changes in FA were not similarly accompanied in terms of extension by changes in RD. Widespread structural alterations in the white matter could prevent good reading ability at word level, which is consistent with recent studies demonstrating the involvement of multiple cortical regions and white matter tracts in reading disabilities.

Connectome hubs at resting state in children and adolescents: Reproducibility and psychopathological correlation.

Functional brain hubs are key integrative regions in brain networks. Recently, brain hubs identified through resting-state fMRI have emerged as interesting targets to increase understanding of the relationships between large-scale functional networks and psychopathology. However, few studies have directly addressed the replicability and consistency of the hub regions identified and their association with symptoms. Here, we used the eigenvector centrality (EVC) measure obtained from graph analysis of two large, independent population-based samples of children and adolescents (7-15 years old; total N=652; 341 subjects for site 1 and 311 for site 2) to evaluate the replicability of hub identification. Subsequently, we tested the association between replicable hub regions and psychiatric symptoms. We identified a set of hubs consisting of the anterior medial prefrontal cortex and inferior parietal lobule/intraparietal sulcus (IPL/IPS). Moreover, lower EVC values in the right IPS were associated with psychiatric symptoms in both samples. Thus, low centrality of the IPS was a replicable sign of potential vulnerability to mental disorders in children. The identification of critical and replicable hubs in functional cortical networks in children and adolescents can foster understanding of the mechanisms underlying mental disorders.

Age-effects in white matter using associated diffusion tensor imaging and magnetization transfer ratio during late childhood and early adolescence.

In the last decade, several studies have described the typical brain white matter maturation in children and adolescents. Diffusion tensor imaging (DTI) is the most frequent MRI technique used to investigate the structural changes across development. However, few previous studies have used the magnetization transfer ratio (MTR), which gives a closer measure of myelin content. Here, we employed both techniques for the same sample of 176 typically developing children from 7 to 14years of age. We investigated the associations between DTI parameters and MTR measure, to assess the myelination in the brain in development. Secondly, we investigated age-effects on DTI parameters (fractional anisotropy, axial, radial and mean diffusivities) and MTR. No significant correlations between MTR and DTI parameters were observed. In addition, a significant age-effect was detected for DTI data but was not visible for MTR data. Thereby, changes in white matter at this age might be primarily correlated with microstructural changes.

Default mode network maturation and psychopathology in children and adolescents.

BACKGROUND: The human default mode (DMN) is involved in a wide array of mental disorders. Current knowledge suggests that mental health disorders may reflect deviant trajectories of brain maturation. METHOD: We studied 654 children using functional magnetic resonance imaging (fMRI) scans under a resting-state protocol. A machine-learning method was used to obtain age predictions of children based on the average coefficient of fractional amplitude of low frequency fluctuations (fALFFs) of the DMN, a measure of spontaneous local activity. The chronological ages of the children and fALFF measures from regions of this network, the response and predictor variables were considered respectively in a Gaussian Process Regression. Subsequently, we computed a network maturation status index for each subject (actual age minus predicted). We then evaluated the association between this maturation index and psychopathology scores on the Child Behavior Checklist (CBCL). RESULTS: Our hypothesis was that the maturation status of the DMN would be negatively associated with psychopathology. Consistent with previous studies, fALFF significantly predicted the age of participants (p < .001). Furthermore, as expected, we found an association between the DMN maturation status (precocious vs. delayed) and general psychopathology scores (p = .011). CONCLUSIONS: Our findings suggest that child psychopathology seems to be associated with delayed maturation of the DMN. This delay in the neurodevelopmental trajectory may offer interesting insights into the pathophysiology of mental health disorders.

Temporal stability of network centrality in control and default mode networks: Specific associations with externalizing psychopathology in children and adolescents.

Abnormal connectivity patterns have frequently been reported as involved in pathological mental states. However, most studies focus on "static," stationary patterns of connectivity, which may miss crucial biological information. Recent methodological advances have allowed the investigation of dynamic functional connectivity patterns that describe non-stationary properties of brain networks. Here, we introduce a novel graphical measure of dynamic connectivity, called time-varying eigenvector centrality (tv-EVC). In a sample 655 children and adolescents (7-15 years old) from the Brazilian "High Risk Cohort Study for Psychiatric Disorders" who were imaged using resting-state fMRI, we used this measure to investigate age effects in the temporal in control and default-mode networks (CN/DMN). Using support vector regression, we propose a network maturation index based on the temporal stability of tv-EVC. Moreover, we investigated whether the network maturation is associated with the overall presence of behavioral and emotional problems with the Child Behavior Checklist. As hypothesized, we found that the tv-EVC at each node of CN/DMN become more stable with increasing age (P < 0.001 for all nodes). In addition, the maturity index for this particular network is indeed associated with general psychopathology in children assessed by the total score of Child Behavior Checklist (P = 0.027). Moreover, immaturity of the network was mainly correlated with externalizing behavior dimensions. Taken together, these results suggest that changes in functional network dynamics during neurodevelopment may provide unique insights regarding pathophysiology.

Decreased centrality of subcortical regions during the transition to adolescence: a functional connectivity study.

Investigations of brain maturation processes are a key step to understand the cognitive and emotional changes of adolescence. Although structural imaging findings have delineated clear brain developmental trajectories for typically developing individuals, less is known about the functional changes of this sensitive development period. Developmental changes, such as abstract thought, complex reasoning, and emotional and inhibitory control, have been associated with more prominent cortical control. The aim of this study is to assess brain networks connectivity changes in a large sample of 7- to 15-year-old subjects, testing the hypothesis that cortical regions will present an increasing relevance in commanding the global network. Functional magnetic resonance imaging (fMRI) data were collected in a sample of 447 typically developing children from a Brazilian community sample who were submitted to a resting state acquisition protocol. The fMRI data were used to build a functional weighted graph from which eigenvector centrality (EVC) was extracted. For each brain region (a node of the graph), the age-dependent effect on EVC was statistically tested and the developmental trajectories were estimated using polynomial functions. Our findings show that angular gyrus become more central during this maturation period, while the caudate; cerebellar tonsils, pyramis, thalamus; fusiform, parahippocampal and inferior semilunar lobe become less central. In conclusion, we report a novel finding of an increasing centrality of the angular gyrus during the transition to adolescence, with a decreasing centrality of many subcortical and cerebellar regions.

Age effects on the default mode and control networks in typically developing children.

BACKGROUND: The investigation of neurodevelopment during late childhood and pre-adolescence has recently attracted a great deal of interest in the field of neuroimaging. One promising topic in this field is the formation of brain networks in healthy subjects. The integration between neural modules characterizes the ability of the network to process information globally. Although many fMRI-based neurodevelopment studies can be found in the literature, the analyses of very large samples (on the order of hundreds of subjects) that focus on the late childhood/pre-adolescence period and resting state fMRI are scarce, and most studies have focused solely on North American and European populations. AIMS: In this study, we present a descriptive investigation of the developmental formation of the Default Mode Network and the Control Network based on a Brazilian, cross-sectional community sample of 447 typically developing subjects aged 7-15 years old. METHODS: Resting state fMRI data were acquired using two MRI systems from the same manufacturer using the same acquisition parameters. We estimated the age effects on the strength of the links (between brain regions) and the network features (graph descriptors: degree and eigenvector centrality). RESULTS: Our findings showed an increase in the antero-posterior connectivity in both studied networks during brain development. The graph analyses showed an increase in centrality with age for most regions in the Default Mode Network and the dorsal anterior and posterior cingulate, the right anterior insula and the left posterior temporal cortex in the Control Network. CONCLUSION: We conclude that the period of 7-15 years of age is crucial for the development of both the Default Mode and Control networks, with integration between the posterior and anterior neuronal modules and an increase in the centrality measures of the hub regions.

Dimorfismo sexual no sistema nervoso central na espécie humana / Sexual dimorphism in the central nervous system in the human species

O estudo dos gêneros masculino e feminino, suas diferenças e seus comportamentos, tem sido fonte de incontáveis questionamentos em várias áreas do conhecimento humano ao longo de toda a história da Humanidade. Diversas especialidades têm estudado o tópico das diferenças entre homens e mulheres, porém esses estudos têm ocorrido de forma dissociada, dificultando a sua compreensão global e suas inter-relações. Partindo desse princípio, esta revisão teve como objetivo estudar a existência da relação entre as estruturas anatômicas do cérebro de pessoas com desenvolvimento normal e suas funcionalidades e os processos de diferenças comportamentais entre os gêneros masculino e feminino. A maioria dos trabalhos publicados entre 1990 e 2004 e aqui analisados é recorrente em suas conclusões ao apontarem diferenças em estruturas anatômicas e funcionais, em várias áreas dos cérebros de homens e mulheres.

The study of the genders, its differences and its behaviors, have been sources of countless questionings in some areas of the human knowledge throughout all the history of the Humanity. Various specialties have studied the topic of the differences between men and women; however these studies have occurred in unassociated ways, rendering difficulty for the global understanding and its relationships. The purpose of this review was to study the existence of relation between the anatomical structures of the brain among people with normal development and functionalities and the different behavior processes between male and female genders. Most of the analyzed papers published between 1990 and 2004 shows the existence of differences in anatomical and functional structures, in several areas of men's and women’s brains.

Dimorfismo sexual no sistema nervoso central na espécie humana / Sexual dimorphism in the central nervous system in the human species

O estudo dos gêneros masculino e feminino, suas diferenças e seus comportamentos, tem sido fonte de incontáveis questionamentos em várias áreas do conhecimento humano ao longo de toda a história da Humanidade. Diversas especialidades têm estudado o tópico das diferenças entre homens e mulheres, porém esses estudos têm ocorrido de forma dissociada, dificultando a sua compreensão global e suas inter-relações. Partindo desse princípio, esta revisão teve como objetivo estudar a existência da relação entre as estruturas anatômicas do cérebro de pessoas com desenvolvimento normal e suas funcionalidades e os processos de diferenças comportamentais entre os gêneros masculino e feminino. A maioria dos trabalhos publicados entre 1990 e 2004 e aqui analisados é recorrente em suas conclusões ao apontarem diferenças em estruturas anatômicas e funcionais, em várias áreas dos cérebros de homens e mulheres. (AU)

The study of the genders, its differences and its behaviors, have been sources of countless questionings in some areas of the human knowledge throughout all the history of the Humanity. Various specialties have studied the topic of the differences between men and women; however these studies have occurred in unassociated ways, rendering difficulty for the global understanding and its relationships. The purpose of this review was to study the existence of relation between the anatomical structures of the brain among people with normal development and functionalities and the different behavior processes between male and female genders. Most of the analyzed papers published between 1990 and 2004 shows the existence of differences in anatomical and functional structures, in several areas of men's and women’s brains. (AU)